ReMM

ReMM prioritizes potentially disease-causal noncoding variants in human genomes by scoring variant pathogenicity using features and variants retrained for the GRCh38 genome build.

Key Features:

• GRCh38 compatibility: Retrained specifically on features and variants mapped to the GRCh38 human genome build to ensure consistency with that reference.
• Robustness to class imbalance: Maintains performance in highly imbalanced datasets typical of rare Mendelian disease variant discovery.
• Cross-build correlation and improved coverage: Scores on GRCh38 show high correlation with the previous GRCh37 release and benefit from enhanced coverage of genomic annotations.
• Prioritization performance: Demonstrates superior performance in comparative analyses for prioritizing noncoding mutations relative to other variation scores in imbalanced datasets.

Scientific Applications:

• Rare Mendelian disease variant prioritization: Prioritizes noncoding variants that may be causative in rare Mendelian disorders.
• Genomic interpretation in research and clinical contexts: Supports interpretation of noncoding variant pathogenicity for genomics and personalized medicine studies.

Methodology:

ReMM was retrained on features and variant sets specific to the GRCh38 genome build, leveraging updated genomic annotations and variant information to produce the GRCh38-based pathogenicity scores.